title: miR-200s contribute to interleukin-6 (IL-6)-induced insulin resistance in hepatocytes.
abstract: By influencing the activity of the PI3K/AKT pathway, IL-6 acts as an important regulator of hepatic insulin resistance. miR-200s have been shown to control growth by regulating PI3K, but the role of miR-200s in the development of hepatic insulin resistance remains unclear. The present study showed that elevated serum concentration of IL-6 is associated with decreased levels of miR-200s, impaired activation of the AKT/glycogen synthase kinase (GSK) pathway, and reduced glycogenesis that occurred in the livers of db/db mice. As shown in the murine NCTC 1469 hepatocytes and the primary hepatocytes treated with 10 ng/ml IL-6 for 24 h and in 12-week-old male C57BL/6J mice injected with 16 μg/ml IL-6 by pumps for 7 days, IL-6 administration induced insulin resistance through down-regulation of miR-200s. Moreover, IL-6 treatment inhibited the phosphorylation of AKT and GSK and decreased the glycogenesis. The effects of IL-6 could be diminished by suppression of FOG2 expression. We concluded that IL-6 treatment may impair the activities of the PI3K/AKT/GSK pathway and inhibit the synthesis of glycogen, perhaps via down-regulating miR-200s while augmenting FOG2 expression.
authors.affiliation: Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Dou
authors.forename: Ting
authors.initials: T
authors.lastname: Zhao
authors.forename: Lilin
authors.initials: L
authors.lastname: Wang
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Huang
authors.forename: Juan
authors.initials: J
authors.lastname: Jiao
authors.forename: Dan
authors.initials: D
authors.lastname: Gao
authors.forename: Hangxiang
authors.initials: H
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Shen
authors.forename: Yong
authors.initials: Y
authors.lastname: Man
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D022781:Hepatocytes / Q000378:metabolism*; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000502:physiology*; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D016133:Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D015850:Interleukin-6; D035683:MicroRNAs; C543719:Mirn200 microRNA, mouse
keywords: AKT; Glycogen; Glycogen Synthase Kinase 3; Interleukin; MicroRNA